A comparison of augmenting central serotonin and noradrenaline function in healthy subjects: implications for studies on the neurochemistry of anxiety

Abstract

Biochemical and psychophysiological effects of augmenting serotonergic and noradrenergic function were compared in 12 normal volunteers. Fluvoxamine (100 mg), a serotonin (5-HT) re-uptake inhibitor, maprotiline (75 mg), a noradrenaline re-uptake inhibitor, and placebo were given for 7 days each to each subject. Subjects were tested pre-drug on days 1, 4 and 8 of each treatment. Catecholamines in 24 h urine, 'platelet-rich' plasma 5-HT and hormones, EEG, auditory evoked response, skin conductance, and bodily and psychological responses were monitored. Augmentation of central 5-HT by fluvoxamine was demonstrated by the decrease of 5-HT plasma levels. Fluvoxamine also reduced urinary dopamine, indicating a decrease in dopamine metabolism in response to augmentation of 5-HT function. Decrease in pulse rate, loss of appetite and a mild arousing effect were also detected with administration of fluvoxamine. Thus, further investigations on the neuro chemistry of anxiety disorders should include the study of mechanisms of interaction of neurotransmitters.